The formation of vascular obstructions in a subject, such as a blood clot or thrombus, can obstruct the flow of blood through the circulatory system and cause significant health problems. Vascular obstructions can form, for example, upon a blood vessel being injured after which the subject's body responds by forming a clot made of thrombocytes and fibrin at the injury site. In other instances, vascular obstructions can form independently of injury to a vessel. For instance, the subject may be genetically predisposed to form blood clots, or blood clots may form as a result of dietary and/or lifestyle choices. Regardless of the etiology, the formation of a vascular obstruction in a subject remains a significant health concern.
For example, deep vein thrombosis (DVT) can is a blood clot that forms in a vein deep in the body. DVT has led to the hospitalization of over 600,000 people in the United States annually. The most serious complication of DVT, referred to as pulmonary embolus, contributes to the death of approximately 200,000 people in the United States annually, and is the third most common cause of cardiovascular related mortality after myocardial infarction and stroke. Symptoms of DVT are collectively referred to as post-thrombotic syndrome (PTS), and include leg heaviness, tiredness, cramping and ulceration.
Conventional therapy for the treatment of vascular obstructions like those that occur with DVT include the administration of anticoagulation medication. However, this method of treatment is based upon a single clinical trial from 1960 in combination with several subsequent observational trials, has changed little since that time. Anticoagulation therapy generally includes treatment with heparin or, more recently, low-molecular-weight heparin, followed by three months of oral anticoagulation therapy. Rather than causing significant fibrinolytic activity, the treatment relies instead on a subject's own fibrinolytic mechanisms (e.g., urokinase activity); thus, anticoagulation therapy generally does not result in the removal or destruction of the thrombus.
Other therapies have emerged to treat vascular obstructions, and some of the most widely used therapies include thrombolytic therapy and catheter directed thrombectomy (CDT). Thrombolytic therapy, or thrombolysis, involves the administration of pharmacological agents that generally result in the increased activation or production of plasmin, a proteolytic enzyme that breaks down fibrin located in a blood clot, thereby dissolving it. Despite the widespread access to thrombolytic therapy, as well as its ability to be rapidly and conveniently administered, drawbacks of thrombolytic therapy include a patency ceiling, low clinical efficacy, and hemorrhagic risk.
Vascular obstructions can also be removed via the use of various thrombectomy procedures. The rationale for this more active removal of a thrombus relies on multiple observations that doing so improves luminal patency, restores valvular function and has the potential to reduce the severity of PTS. Despite these advantages, thrombectomy procedures are usually emergency surgical procedures, often viewed as a last resort, because they generally involve a risk of distal embolization and blood loss during extraction of the thrombus. Additionally, a highly adherent thrombus can be very difficult to remove without causing potential damage to the surrounding vessel.
Therefore, given that thrombolysis often fails to completely remove vascular obstructions, and given that thrombectomy procedures often cause tissue damage in surrounding blood vessels, there is need for more efficacious methods and systems for treating thrombosis.